The inhibition of Spleen Tyrosine Kinase (Syk) activity may be useful for treating certain types of cancer and autoimmune diseases. One such compound that has been found to inhibit Syk activity is represented by Formula I:
or a pharmaceutically acceptable salt thereof. This compound and its synthesis have been described in U.S. Pat. Nos. 8,450,321 and 8,455,493, which are hereby incorporated herein by reference in their entirety, and are hereby incorporated by reference specifically with reference to Examples 1 and 2.
Early clinical oral formulations have involved the use of a mono-mesylate salt of the compound of Formula I. Various challenges, however, have been observed in early clinical studies when this oral formulation was administered to human subjects. First, high inter-subject variability has been observed, which could lead to variable pharmacodynamic responses in subjects. Second, significant drug-drug-interaction and pH effect have been observed with acid suppressants, and it is desired to minimize such observed drug-drug-interaction. Third, a dose-dependent food effect has been observed, and it is also desired to minimize such effect. Fourth, it is desired to improve oral bioavailability.
What is desired in the art are physically stable forms of the compound of Formula I, or a pharmaceutically acceptable salt thereof, that address each of these challenges and facilitate manufacturing processes.